Treacher Collins syndrome (TCS), variably known as mandibulofacial dysostosisand Franceschetti-Klein-Zwahlen syndrome, is one of a number of congenitalcraniofacial abnormalities characterized by malformation of the derivativesof the first and second branchial arches. Though first described by Berry1 in 1889, the definition of the syndrome underwentfurther revision and classification by Franceschetti and Klein in 1949.2
The major features of the complete syndrome include bilateral hypoplasiaof the mandible and zygoma, antimongoloid slanting of the palpebral fissures,micrognathia, beaked nose, malformed ears, and conduction deafness. Colobomataof the lateral lower eyelids are frequently seen, and for this reason, ophthalmologistsare often consulted as part of the multidisciplinary team serving these patients.Other ocular findings, such as cataract, microphthalmos, and atresia of thelacrimal canals, are seen much less frequently.3
Although cataract has been reported in the literature as an infrequentfeature of TCS, the time of onset and morphological features of such cataractshave not been previously described. We present a case of TCS notable for delayedonset of bilateral cataracts that developed after the first year of life.
A 1-month-old girl was referred for evaluation of abnormal eyelids.She was a healthy, full-term, 2400-g infant, the first child born to a healthy20-year-old mother who had no complications during pregnancy. At birth, notchesof the lower eyelid were noted, and she was referred for evaluation. Therewas no family history of ocular disease or congenital syndromes. On examination,she was found to have bilateral lower eyelid colobomas involving the lateralthird of the inferior lids (Figure 1).There were no periocular dermoids, no corneal limbal dermoids, no cataracts,and no optic nerve hypoplasia or ocular colobomas. The remainder of the ophtal- micexamination was unremarkable. She was also found to have malar hypoplasia.Given this facial appearance, the diagnosis of TCS was considered. The patientwas evaluated by the Department of Medical Genetics, which confirmed thisdiagnosis. The child did well until 13 months of age when the parents beganto notice cloudiness in the pupils of both eyes. On ophthalmic examination,she was found to have bilateral nuclear cataracts precluding view of the posteriorpole in each eye (Figure 2). There wasa small rim of clear cortex peripherally. Nys tagmus was not present.The patient underwent bilateral extracapsular cataract extraction with posteriorchamber lens implantation without complication.
On examination, the patient was foundto have bilateral lower eyelid colobomas involving the lateral third of theinferior lids.
On ophthalmic examination, the patientwas found to have bilateral nuclear cataracts precluding view of the posteriorpole in each eye.
Treacher Collins syndrome is a congenital craniofacial abnormality thataffects approximately 1 in 50 000 live births. It is transmitted by autosomaldominant inheritance with high penetrance and variable expressivity, thoughapproximately 60% of cases occur with no family history and are thought toarise by de novo mutation.
The pathogenesis of TCS was initially thought to be due to defectiveossification of the facial bones. However, the common derivation of the affectedtissues from the first and second branchial arches led to speculation thatdefects in neural crest cell migration might be responsible.4 Morerecently, it has been suggested that premature cell death in the ectodermalplacodes of the first and second branchial arches, rather than impaired migrationof neural crest cells, may instead be the pathogenetic mechanism.5
The gene responsible for TCS has recently been cloned, and a proteinproduct has been identified with homology to a family of nucleolar-cytoplasmictransport proteins.6 Almost all mutationsidentified in TCS result in premature termination of the protein product,suggesting that the pathogenetic effects result from haploinsufficiency ofthe gene product during embryogenesis. The precise function of this proteinproduct and its role in TCS pathogenesis remain unknown. As a result of thisresearch, a genetic test for prenatal diagnosis in affected families is nowavailable.
Of note, the prevalence of cataracts is variable in other craniofacialsyndromes involving malformation of the first and second branchial arches.They are seen very frequently in Hallerman-Streiff syndrome, occasionallyin Pierre Robin syndrome, and are absent in Goldenhar syndrome.7
Though the literature refers to cataract as an infrequent ophthalmicfinding in TCS, no specific caseswith cataract could be identified. Therewere no cataracts mentioned in 2 recent case series that examined the ocularfindings in 14 and 24 patients with TCS, respectively.8,9
To our knowledge, this is the first reported case of delayed-onset infantilecataracts in TCS. It is significant because this child displayed no signsof cataract at birth or at 10 months of age but developed bilateral, visuallysignificant cataracts by 13 months of age. The possibility that delayed-onsetcataracts can develop rapidly in infants with TCS suggests that more frequentophthalmologic follow-up and detailed anticipatory guidance to parents arewarranted to prevent the possibility of undetected cataracts leading to irreversibleamblyopia.
Correspondence: Dr Fredrick, Departmentof Ophthalmology, University of California, San Francisco, 10 Koret Way, Box0730, San Francisco, CA 94143-0730 (email@example.com).
Financial Disclosure: None.
Biebesheimer JB, Fredrick DR. Delayed-Onset Infantile Cataracts in a Case of Treacher Collins Syndrome. Arch Ophthalmol. 2004;122(11):1721-1722. doi:10.1001/archopht.122.11.1721